Holmium-166 Radioembolization of Hepatic Metastases in Salvage Setting: Preliminary Findings from a Single Center Experience

Abstract

Purpose The aim of this study is to report the early outcomes of holmium-166 (¹⁶⁶Ho) radioembolization in the treatment of liver metastases.

Methods Nine patients with liver metastases originating from different primary sites were treated with ¹⁶⁶Ho radioembolization between January 2019 and February 2020. The patients were assessed for pain using a visual analog scale (VAS) and quality of life (QoL) at various intervals during hospitalization and follow-up. Toxicity that may be attributable to radioembolization was graded according to CTCAE v5.0. The tumor dosimetry and tumor response were assessed with anatomic and metabolic imaging.

Results The mean tumor dose was 150 Gy, 95% confidence interval (CI) was 135.2 to 164.8, with a range of 100 to 200 Gy based on single-photon emission computed tomography (SPECT)/CT, and distribution verified with inline T2/R2* magnetic resonance imaging (MRI) maps. No early (30-day) mortality or grade greater than 2 toxicities were noted, but one patient had chylous ascites. QoL assessed with the European Quality of Life 5-Dimensions 3-Level version (EQ-5D-3L) revealed mean index scores of 0.748 (range: 0.5–1), 95% CI of 0.6 to 0.9, before the procedure, and 0.7 (range: 0.5–1) and 95% CI of 0.6 to 0.8, at 1 month. The mean VAS was 70.6, 95% CI was 65.5 to 75.6, immediately after the procedure, and decreased to the mean VAS of 65.7 and 95% CI of 55.9 to 75.5 after 1 month. Five patients showed a partial response, three showed a stable disease, and one showed progressive disease at the first 2- to 3-month imaging follow-up.

Conclusion Radioembolization with ¹⁶⁶Ho microspheres for liver metastases appears to be safe, tolerable, and effective during the short term in this small-scale study.

Keywords

holmium-166 microspheres - radioembolization - liver metastases

Introduction

The first description of the use of holmium-166 (¹⁶⁶Ho) for radioembolization of hepatic malignancies was described by Nijsen et al.[1] ¹⁶⁶Ho is a highly paramagnetic metal element that enables biodistribution and quantification on magnetic resonance imaging (MRI) with a good correlation with single-photon emission tomography (SPECT).[2] [3] Besides β particles, ¹⁶⁶Ho emits gamma photons that can be visualized under SPECT facilitating treatment dosimetry.[4] [5] After receiving the European CE mark recently, ¹⁶⁶Ho was introduced in a limited number of patients and centers.[6] We aimed to report our experience with ¹⁶⁶Ho radioembolization in the treatment of liver metastasis.

Materials and Methods

Between January 2019 and February 2020, nine patients (six females and three males; mean age ± standard deviation: 56.3 ± 11.9 years) with metastatic liver lesions of different primary origins were treated with ¹⁶⁶Ho microspheres. Patients with liver only disease or stable extrahepatic metastatic disease and liver predominant disease, who were chemoresistant and unsuitable for other types of locoregional therapy, were included in the study. A multidisciplinary institutional gastrointestinal tumor board proposed the treatment beforehand. The exclusion criteria were similar to ⁹⁰Y radioembolization.[7] This is a retrospective case cohort study, which was approved by the institutional ethical committee (protocol number 21–159), and all the procedures were performed in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from all the participants.

Radioembolization with ¹⁶⁶Ho

Mapping angiography and treatment angiography were performed using a 2.7-Fr microcatheter or a 2.8-Fr temporary occlusion balloon catheter (Progreat or Occlusafe; Terumo, Tokyo, Japan), which was placed through a 5-Fr standard catheter. A scout dose of ^99mTc-macroaggregated albumin (^99mTc-MAA; 50–150 MBq) depending on the perfused liver volume was administered and assessed using SPECT (Siemens e.cam Signature, Siemens Medical Solutions, Erlangen, Germany). Two weeks later, ¹⁶⁶Ho-loaded poly (L-lactic acid) microspheres (QuiremSpheres, Quirem Medical B.V., Deventer, the Netherlands) with a maximum whole-liver dose of 60 Gy were administered based on the Holmium Embolization Particles for Arterial Radiotherapy (HEPAR) trial.[8] The procedure was performed according to the guidelines of Cardiovascular and Interventional Radiological Society of Europe (CIRSE).[9]

Just before and after the procedure, T2* fl2D images with 16 echoes with a starting echo time (TE) value of 1.5 milliseconds, a repetition time (TR) of 175 milliseconds, and a flip angle of 35 degrees were obtained. The distribution of paramagnetic ¹⁶⁶Ho microspheres was inspected by signal loss under MRI (MAGNETOM Skyra 3T, Siemens, Erlangen, Germany) after the procedure.[10] Tumor dosimetry was performed using SPECT images taken 3 days after the treatment. Inline T2* and R2* maps derived from MRI were evaluated qualitatively and quantitatively in comparison with SPECT.

Postprocedural Evaluation

This study classified any acute or chronic hepatotoxicity attributable to radioembolization but not disease progression or any associated therapies using laboratory and clinical findings based on CTCAE v5. Radioembolization-induced liver disease (REILD) was evaluated with a clinical presentation of jaundice, ascites, and a bilirubin increase over 2.92 mg/dL besides further definitions such as sinusoidal obstruction and hepatic necrosis.[11] [12]

Patients were assessed for pain using a visual analog scale (VAS) before the procedure and at 2- to 4-hour intervals after the procedure in the first 24 hours. The maximum VAS pain scores during hospitalization compared with the preprocedural VAS pain scores with an increase of at least one were considered procedure related. Patients did not receive any nonmandatory premedication, and postembolization syndrome findings were managed on a symptom basis approach. Quality of life (QoL) was assessed with the EuroQol 5-Dimensions (EQ-5D) questionnaire, which assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.[13] A single index score and VAS were calculated at baseline and at 1 month.

The procedure was performed by an interventional radiologist and a nuclear medicine physician with 8 years of experience in performing radioembolization; they also evaluated the follow-up images. To evaluate the tumor response after radioembolization, in addition to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) with MRI, the metabolic response with a reduction in glycolysis on fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was also considered in proper patients.[14] [15]

Results

Nine patients who received radioembolization with ¹⁶⁶Ho microspheres had intrahepatic metastases originating from different primary sites ([Table 1]). All patients had multiple metastases (>5), except for one who had two metastases. The mean size of the index lesions was 33 mm (smallest 10 mm and largest 123 mm). Patients had preserved liver function based on laboratory tests and sufficient performance status before treatment.

Table 1 Patient and treatment characteristics

Primary site	Age/gender	Adjunct treatments	t number/size[a]	166Ho TARE approach and dose[b]	Response[c]
Ovary ca	61/F	Paclitaxel + carboplatin, Caelyx + carboplatin, + bevacizumab TACE to LL (post-)	Multiple >5/15–12–11 mm	RL 40 Gy (150–175 Gy)	Stable
Colon ca	37/F	Metastasectomy RL FOLFOX + cetuximab, FOLFIRI + cetuximab, RFA to LL FOLFIRI + bevacizumab, irinotecan + bevacizumab Folinat-FU-cisplatin + VEctibix, LOnsurf	2/65 and 35 mm	LL 60 Gy (170–180 Gy)	Partial
Gastric ca	70/F	Herceptin + paclitaxel TACE to LL (post-)	Multiple >5/123–63–67 mm	RL 60 Gy (170–200 Gy)	Stable
Pancreas ca	58/M	FOLFIRINOX, capecitabine RFA and TACE to RL (post-)	Multiple >5/31–24–23 mm	RL 45 Gy (100–170 Gy)	Partial
Uveal melanoma	60/F	Paclitaxel + carboplatin 90 Y to RL	Multiple >5/13–10–10 mm	LL segments 2–3 and 4 60 Gy	Partial
Breast ca	61/F	Tamoxifen, Ibrance + Arimidex, docetaxel + Herceptin + Perjeta, capecitabine + vinorelbine	Multiple >5/45–27–25 mm	RL and segment 4 60 Gy (110–190 Gy)	Partial
Colangio ca	33/F	GEMOX mFOLFIRI	Multiple >5/29–23–17 mm	RL 40 Gy (110–130 Gy)	Stable
Colon ca	66/M	FOLFOX + bevacizumab RFA Capecitabin, FOLIRI-aflibercept, regorafenib	Multiple >5/39–17–13 mm	RL segments 5 and 6, 55 Gy (150–170 Gy) LL 55 Gy (135–170 Gy)	Partial
Pancreas ca	61/F	FOLFORINOX, GEMOX, FOLFIRI, docetaxel + gemcitabine RFA to LL (post-)	Multiple >5/48–42–28 mm	RL and segment 4 60 Gy (100–120 Gy)	Progression

Abbreviations: ca, cancer; F, female; LL, left lobe; M, male; t, tumor; RL, right lobe; RFA, radiofrequency ablation; TACE, transarterial chemoembolization.

^a Three index lesions if multiple.

^b Absorbed liver doses versus tumoral doses in () according to posttreatment dosimetry.

^c Respond assessed with RECIST 1.1 criteria and mRECIST where appropriate.

All but one patient had a bilobar disease; however, none of the patients received whole-lobar ¹⁶⁶Ho radioembolization during the single-session treatments. One patient had ⁹⁰Y radioembolization, four of the patients had radiofrequency ablation (RFA), and three had transarterial chemoembolization (TACE) separately before or after a time ranging from 3 weeks to 6 months. They all had previously received first-line chemotherapy regimens according to their primary disease. Six patients received unilobar treatment, and three patients received bilobar multisegmental treatment with split doses. In three patients, the standard dose of 60 Gy could not be administered due to the embolization effect creating a sluggish flow. The mean absorbed liver dose was 54.1 Gy, 95% confidence interval (CI) of 49.2 to 59, in 11 doses, including two split doses. The mean tumor dose was 150 Gy, 95% CI (135.2–164.8), with a minimum of 100 Gy and a maximum of 200 Gy. In one patient with uveal melanoma, tumor dosimetry SPECT could not be performed, as she was lost to follow-up after treatment. In all patients including the former one, the distribution of microspheres was confirmed with MRI using T2* and R2* maps ([Fig. 1]). The mean follow-up period after ¹⁶⁶Ho radioembolization was 10.4 ± 3.17 months. One patient died 9 months after the procedure due to disease progression. One patient was lost to follow-up during the pandemic 6 months after the procedure. Five patients showed a partial response, three had stable disease, and one had progressive disease at the first follow-up.

Fig. 1 A 37-year-old man with colorectal liver metastases. (A) Contrast-enhanced T1-weighted image showing a mass in the left lobe. (B) T2* and corresponding (C) T2* map (ms) showing increased paramagnetism in the left lobe and the tumor after ¹⁶⁶Ho radioembolization. (D) Corresponding posttreatment single-photon emission computed tomography (SPECT) fused on magnetic resonance imaging (MRI).

Clinical and laboratory results during a 3-month follow-up were reviewed to assess treatment-related adverse events. Two cases of grade 3 pain, two cases of grade 3 nausea (in the same two patients), and no cases of early (30-day) mortality were identified. No grade greater than 2 toxicities was observed after the early period ([Table 2]). In one patient, grade 3 delayed hepatobiliary toxicity with bilirubin levels greater than 3 mg/dL and intractable chylous ascites occurred within 6 weeks.

Table 2 Follow-up according to CTCAE v5 and QOL besides VAS pain

	Pre-op	First 24 h	1 d post-op	1 mo post-op	3 mo post-op
Mean index score VAS (EQ-5D-3L)	0.748 70.555	–	–	0.717 65.666	–
Pain VAS (n)	–	9–10 (4), 6 (2), 3 (1), 0 (2)	3 (2), 4 (1), 0 (3), Grade 3 (2)	3 (1), 2(1)	–
Fever (n)	–	(2)	–	–	–
Nausea (n)	–	(4)	Grade 3(2)	–	–
Fatigue (n)	–	(9)	8	2
Ascites (n)	–	–	–	Grade 3 (1)	Grade 3 (1)
Hyperbilirubinemia (n)	–	–	–	Grade 1	Grade 2
Hypoalbuminemia (n)	–	–	–	–	–
REILD (n)	–	–	–	–	–

Abbreviations: EQ-5D-3L, European Quality of Life 5-Dimensions 3-Level version; QOL, quality of life; REILD, radioembolization-induced liver disease; VAS, visual analog scale.

Immediately after the procedure, four patients had a pain VAS score of 9 to 10, which was relieved by patient-controlled morphine analgesia. The mean VAS in the first 24 hours was 5.8, 95% CI (3.2–8.3). Only two patients required extra analgesics or extended hospitalization because of pain after the procedure; these two patients were treated with split doses toward larger volumes of liver parenchyma.

QoL was assessed with EQ-5D-3L, which revealed mean index scores of 0.748 (range: 0.507–1), 95% CI (0.6–0.9), before the procedure and 0.7 (range 0.5–1), 95% CI (0.6–0.8), at 1 month. The mean VAS score was 70.6, 95% CI (65.5–75.6), immediately after the procedure and decreased to 65.7, 95% CI (55.9–75.5), 1 month after the procedure. Better index scores and VAS scores before radioembolization corresponded to better scores after the procedure.

Discussion

Although patients with liver metastases were successfully treated with ¹⁶⁶Ho radioembolization during the phase 1 and 2 studies of the HEPAR trials, multicenter experiences are still lacking related to real-world patients.[8] [16] In this study, we investigated the feasibility of ¹⁶⁶Ho radioembolization for hepatic metastases in salvage settings. The patients had liver tumor involvement due to different primary cancers; accordingly, they also received various treatments, such as surgical ablation and embolization, in addition to systemic chemotherapy. ¹⁶⁶Ho radioembolization was associated with limited toxicity during the early period except for one case. Five patients showed a partial response, three showed stable disease, and one showed progressive disease at the first 2- to 3-month imaging follow-up. After the procedure, the patients were successfully treated for pain and postembolization syndrome during the first 24 hours. Compared with the preoperative QoL, the postoperative QoL was not obviously different during the clinical follow-up.

In their single-center study with ¹⁶⁶Ho radioembolization, Radosa et al reported no grade greater than 3 postembolization syndrome in three of nine patients with bilobar involvement of hepatocellular carcinoma (HCC) and corresponding bilobar treatment.[6] The results in their small cohort were comparable to those in ⁹⁰Y radioembolization studies performed with glass microspheres and resin microspheres.[17] [18] When the latter two studies with two different microspheres were compared for radioembolization of HCC, the rate of postembolization syndrome was as high as 53% with resin microspheres and in similar ranges (2.5–5.9% at maximum) within 3 months in both studies. According to CTCAE v5, our study had two grade 3 cases of pain and two grade 3 cases of nausea, leading to prolongation of two patients' hospitalization. Given the heterogeneity of the patients, the multiplicity of the tumors and possible prior systemic chemotherapy side effects may also have contributed to the severity of the postembolization syndrome in our study. Prince et al reported grade 3 or 4 adverse events, with abdominal pain (18%) and nausea (8%) being the most common among a total of 37 metastatic liver patients after ¹⁶⁶Ho radioembolization procedures.[8] These findings are also comparable to those of Benson et al, who performed ⁹⁰Y radioembolization in 151 liver patients with liver metastases of several origins.[19]

No grade greater than 2 toxicities were observed after the early period, and no early (30-day) mortality was noted. One patient had a grade 3 delayed hepatobiliary toxicity, which may have been attributable to disease progression in the setting of progressive metastatic disease in the untreated segments of the liver.

Despite recent advances in tumor-directed therapies, such treatments are not without toxicities, and up to 95% of cancer patients consider the possible side effects of treatment to be as significant as survival.[20] van Roekel et al reported that the QoL did not change significantly in patients with liver metastases treated with ¹⁶⁶Ho radioembolization during the HEPAR trials.[21] They also reviewed the effect of Y⁹⁰-RE on the QoL in 14 studies with different liver malignancies and found similar results. In only two studies, including one on HCC and another on colorectal metastases, the QoL deteriorated after Y⁹⁰ radioembolization.[22] [23] We analyzed the QoL at 1 month, as the QoL was affected in the first weeks posttreatment due to postembolization syndrome.[20] Similarly, in our study, a better index score and VAS score before radioembolization resulted in better scores after the procedure. Our data were not sufficiently large to produce statistically significant results. However, many factors should also be considered in metastatic liver patients, such as age, sex, cancer type, performance status symptoms, and extrahepatic disease, as they can affect the QoL.[16] [24] [25]

We performed ¹⁶⁶Ho radioembolization in 11 doses with the intent of achieving the maximum allowed liver absorbed dose of 60 Gy. Local control of the tumor was achieved in all but one patient during the follow-up. The major limitation of this study was the small sample size and heterogeneous cohort of liver metastases to determine the efficacy and feasibility. Yet, there are only a few reports published with ¹⁶⁶Ho radioembolization including HEPAR studies and a study focusing on nine cases of HCC. The novelty of the treatment might justify the need for small single-center studies before larger-scale multicenter prospective studies are designed.

After calculation with SPECT, the tumor dose was found to be between 100 and 200 Gy, while the liver dose was maintained below 60 Gy in our patients. As they were approved at later stages of this study, neither the Q-Suite software platform enabling evaluation of MRI signal loss due to T2* relaxation time shortening based on gradient echo sequences acquired with multiple echo times nor QuiremScout consisting of identical low-energy ¹⁶⁶Ho microspheres was used. This was another limitation of our study. Although performing ¹⁶⁶Ho radioembolization using ^99mTc-MAA for the scout dose, SPECT, and MRI for dosimetry is feasible, the aforementioned CE-marked techniques may increase the consistency and quality of treatment. Inline R2* maps derived from MRI were used to calculate doses manually in our patients, and simplistic dosimetry calculations were performed comparable to SPECT dosimetry results. However, further discussion of these results is beyond the scope of this study since our method is not validated. Due to high energy caused by gamma emissions along with β particles that are considered suitable for internal radionuclide therapy, patients generally undergo SPECT on days 3 to 5 after ¹⁶⁶Ho radioembolization to prevent image degradation and noise. The distribution of the microspheres in relatively small volumes or with cystic necrotic components could be confirmed with qualitative assessment of MR images. This distribution was visualized under MRI up to several months after radioembolization, as it is independent of activity ([Fig. 2]).

Fig. 2 A 61-year-old woman with breast cancer liver metastases. (A) Diffusion weighted image magnetic resonance (MR) showing hyperintense lesions. (B) T1-weighted multigradient echo image showing paramagnetic ¹⁶⁶Ho microspheres in the liver persisting 3 months after radioembolization with some shrinkage of the tumors.

In three patients who had tumors with relatively small volumes, cystic necrotic components, and relatively hypovascular characteristics, the standard dose could not be administered due to the embolization effect creating a sluggish flow. Early stasis during radioembolization with resin microspheres has been reported in 20% of patients and even more frequently (38%) in patients receiving multiple prior lines of chemotherapy, such as those with colorectal cancer liver metastases.[26] [27] ¹⁶⁶Ho microspheres have more particles and may have a more significant embolic effect than glass microspheres, similar to resin microspheres, which might also be true when managing relatively hypovascular and necrotic liver tumors such as metastases.[28] On the other hand, more particles, resulting in a more uniform particle distribution in a tumor, may be beneficial for larger tumor volumes or more hypervascular tumors and for multiple tumors.[29]

Conclusion

¹⁶⁶Ho microspheres in radioembolization for liver metastases with diverse origins in patients with a history of resection, ablation, chemoembolization, and ongoing chemotherapy appear to be safe, tolerable, and effective.

Conflict of Interest

None declared.

Ethical Approval

This is a retrospective case cohort study, which was approved by the institutional ethical committee (protocol number 21–159). Written informed consent was obtained from all the participants.

• References

• 1 Nijsen JF, Zonnenberg BA, Woittiez JR. et al. Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques. Eur J Nucl Med 1999; 26 (07) 699-704
• 2 Elschot M, Nijsen JFW, Lam MGEH. et al. (⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres. Eur J Nucl Med Mol Imaging 2014; 41 (10) 1965-1975
• 3 Smits MLJ, Dassen MG, Prince JF. et al. The superior predictive value of ¹⁶⁶Ho-scout compared with ^99mTc-macroaggregated albumin prior to ¹⁶⁶Ho-microspheres radioembolization in patients with liver metastases. Eur J Nucl Med Mol Imaging 2020; 47 (04) 798-806
• 4 Smits ML, Elschot M, van den Bosch MA. et al. In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies. J Nucl Med 2013; 54 (12) 2093-2100
• 5 van de Maat GH, Seevinck PR, Elschot M. et al. MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation. Eur Radiol 2013; 23 (03) 827-835
• 6 Radosa CG, Radosa JC, Grosche-Schlee S. et al. Holmium-166 radioembolization in hepatocellular carcinoma: feasibility and safety of a new treatment option in clinical practice. Cardiovasc Intervent Radiol 2019; 42 (03) 405-412
• 7 Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodologic considerations. J Vasc Interv Radiol 2006; 17 (08) 1251-1278
• 8 Prince JF, van den Bosch MAAJ, Nijsen JFW. et al. Efficacy of radioembolization with ¹⁶⁶Ho-microspheres in salvage patients with liver metastases: a phase 2 study. J Nucl Med 2018; 59 (04) 582-588
• 9 Mahnken AH, Spreafico C, Maleux G, Helmberger T, Jakobs TF. Standards of practice in transarterial radioembolization. Cardiovasc Intervent Radiol 2013; 36 (03) 613-622
• 10 Nijsen JF, Seppenwoolde JH, Havenith T, Bos C, Bakker CJ, van het Schip AD. Liver tumors: MR imaging of radioactive holmium microspheres—phantom and rabbit study. Radiology 2004; 231 (02) 491-499
• 11 Sangro B, Gil-Alzugaray B, Rodriguez J. et al. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 2008; 112 (07) 1538-1546
• 12 Braat MN, van Erpecum KJ, Zonnenberg BA, van den Bosch MA, Lam MG. Radioembolization-induced liver disease: a systematic review. Eur J Gastroenterol Hepatol 2017; 29 (02) 144-152
• 13 EuroQol Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy 1990; 16 (03) 199-208
• 14 Akinwande O, Philips P, Scoggins CR. et al. Comparison of tumor response assessment methods in patients with metastatic colorectal cancer after locoregional therapy. J Surg Oncol 2016; 113 (04) 443-448
• 15 Jongen JMJ, Rosenbaum CENM, Braat MNGJA. et al. Anatomic versus metabolic tumor response assessment after radioembolization treatment. J Vasc Interv Radiol 2018; 29 (02) 244-253.e2
• 16 Smits ML, Nijsen JF, van den Bosch MA. et al. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol 2012; 13 (10) 1025-1034
• 17 Mazzaferro V, Sposito C, Bhoori S. et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013; 57 (05) 1826-1837
• 18 Golfieri R, Bilbao JI, Carpanese L. et al; European Network on Radioembolization with Yttrium-90 Microspheres (ENRY) study collaborators. Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma. J Hepatol 2013; 59 (04) 753-761
• 19 Benson III AB, Geschwind JF, Mulcahy MF. et al. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013; 49 (15) 3122-3130
• 20 Meropol NJ, Weinfurt KP, Burnett CB. et al. Perceptions of patients and physicians regarding phase I cancer clinical trials: implications for physician-patient communication. J Clin Oncol 2003; 21 (13) 2589-2596
• 21 van Roekel C, Smits MLJ, Prince JF, Bruijnen RCG, van den Bosch MAAJ, Lam MGEH. Quality of life in patients with liver tumors treated with holmium-166 radioembolization. Clin Exp Metastasis 2020; 37 (01) 95-105
• 22 Steel J, Baum A, Carr B. Quality of life in patients diagnosed with primary hepatocellular carcinoma: hepatic arterial infusion of cisplatin versus 90-yttrium microspheres (TheraSphere). Psychooncology 2004; 13 (02) 73-79
• 23 Wasan HS, Gibbs P, Sharma NK. et al; FOXFIRE trial investigators, SIRFLOX trial investigators, FOXFIRE-Global trial investigators. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol 2017; 18 (09) 1159-1171
• 24 Kim AY, Frantz S, Brower J, Akhter N. Radioembolization with yttrium-90 microspheres for the treatment of liver metastases of pancreatic adenocarcinoma: a multicenter analysis. J Vasc Interv Radiol 2019; 30 (03) 298-304.e2
• 25 Riaz A, Awais R, Salem R. Side effects of yttrium-90 radioembolization. Front Oncol 2014; 4: 198
• 26 Piana PM, Bar V, Doyle L. et al. Early arterial stasis during resin-based yttrium-90 radioembolization: incidence and preliminary outcomes. HPB (Oxford) 2014; 16 (04) 336-341
• 27 Sofocleous CT, Violari EG, Sotirchos VS. et al. Radioembolization as a salvage therapy for heavily pretreated patients with colorectal cancer liver metastases: factors that affect outcomes. Clin Colorectal Cancer 2015; 14 (04) 296-305
• 28 Sato K, Lewandowski RJ, Bui JT. et al. Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol 2006; 29 (04) 522-529
• 29 Boas FE, Bodei L, Sofocleous CT. Radioembolization of colorectal liver metastases: indications, technique, and outcomes. J Nucl Med 2017; 58 (Suppl. 02) 104S-111S

Publication History

Article published online:
11 September 2023